Phase I/II Trial of R-CHOP + Azacytidine in Diffuse Large B Cell Lymphoma

This study is currently recruiting participants.
Verified March 2011 by Weill Medical College of Cornell University

First Received on October 29, 2009.  
Last Updated on March 8, 2011  
History of Changes
This Clinical Trial Sponsored By: Weill Medical College of Cornell University
Collaborator: Celgene Corporation
Information provided by: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01004991
 

Purpose for Clinical Trial

This is a phase I/II open label, multi-center study of azacytidine in combination with standard RCHOP therapy in patients with DLBCL. Patients will be treated with azacytidine at escalating doses on days 1-5, followed by standard dose rituximab plus CHOP chemotherapy on day 8, every 21 days. Patients will be treated for a total 6 cycles. The phase II portion will then evaluate efficacy of the combination at the established MTD.

Condition Study Intervention Phase
Diffuse Large B Cell Lymphoma Biological: rituximab
Drug: cyclophosphamide
Drug: vincristine
Drug: doxorubicin
Drug: prednisone
Drug: azacytidine
Phase 1
Phase 2

Study Type: Study Interventional
Study Design: Study Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Azacytidine + R-CHOP in Diffuse Large B-Cell Lymphoma

Resource links provided by NLM:

MedlinePlus related topics:
Lymphoma
Drug Information available for:
Cyclophosphamide
Prednisone
Azacitidine
Vincristine sulfate
Doxorubicin
Doxorubicin hydrochloride
Rituximab

U.S. FDA Resources

Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures For Clinical Trial:

  • The primary endpoint for the phase I portion of the study is to determine the maximum tolerated dose and toxicity of azacytidine when given in combination with a standard dose (q 21 day) regimen of R-CHOP in patients with DLBCL. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures For Clinical Trial:

  • The primary endpoint for the phase II portion of the study will be progression-free survival(PFS), as measured from the start of the treatment to the date of either documentation of disease progression or death. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 46
Study Start Date: January 2010
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)

Arms

Assigned Study Interventions

Experimental: All patients

subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment – all will receive standard dose RCHOP
Biological: rituximab

375 mg/m2 on Day 8 of each of 6 cycles

Drug: cyclophosphamide

750 mg/m2 on Day 8 of each of 6 cycles

Drug: vincristine

1.4 mg/m2 on Day 8 of each of 6 cycles

Drug: doxorubicin

50 mg/m2 on Day 8 of each of 6 cycles

Drug: prednisone

100 mg PO days 8-12 of each of 6 cycles

Drug: azacytidine

Dose level 1: azacytidine 25 mg/m2 days 1-5 Dose level 2: azacytidine 50 mg/m2 days 1-5 Dose level 3: azacytidine 75 mg/m2 days 1-5

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically confirmed DLBCL with characteristic immunophenotypic profiles. Tumor tissue must be confirmed to express the CD20 antigen by flow cytometry or immunohistochemistry.
  • Patients must have at least one site of measurable disease, 1.5 cm in diameter or greater.
  • Patient has not had any previous treatment.
  • Stage II (not appropriate for abbreviated chemoimmunotherapy and radiotherapy), III or IV disease
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Patients must have laboratory test results within these ranges:

    • Absolute neutrophil count > = 1500/mm³
    • Platelet count > = 75,000/mm³
    • Serum creatinine < = 1.5X upper limit of normal (ULN)
    • Total bilirubin < = 1.5X ULN. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.
    • AST (SGOT) and ALT (SGPT) < = 2 x ULN
  • Disease free of prior malignancies for > = 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
  • Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment.
  • Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacitidine. The effects of azacytidine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Age >18 years.
  • Ability to understand and the willingness to sign a written informed consent document.
  • ECOG performance status of 0-2

Exclusion Criteria:

  • Patients must not have any serious medical condition, laboratory abnormality,or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Patients must not have any condition, including the presence of laboratory abnor

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